I don’t know about you, but it seems like time is speeding up these days – some say the older you get the faster time flies—personally, I flatly reject that theory! But it does seem like just yesterday that I was sitting on this same chair and writing on this same computer about the top news stories of 2008. At any rate, compiling a list of the top stories has become a tradition here at HCSP/HCV Advocate and I’m always eager to hear about what the staff of HCSP and fellow HCV advocates voice as the most newsworthy items of the year. 2009 provided us all with some amazing news stories and it was difficult to tweak them down to a manageable size; however, we have compiled the following list that we believe contains some of the top news stories—items number one and number two are in what we believe is the order of importance—the remaining items are not in any particular order.

HEALTH CARE REFORM

Back in 2008 I wrote about the possibility of healthcare reform in the United States:

“In 2008 we believe that there will be more movement towards health care reform on a local and state level as we have seen in Massachusetts and San Francisco. We all believe that the time is right for major health care reform in this country and that eventually there will be a national focus on health care reform, but it is going to take many years and much advocacy on the part of all Americans to make health care and services for all Americans a reality.”

What we all thought would take many years to accomplish is now close to becoming a reality on a national level. We all need to advocate for this important legislation even though it is far from perfect. Hopefully, once a healthcare measure is passed it can be built upon in the future to ensure that every American has access to quality medical care. So even though the issue about health reform is not specifically hepatitis C-related, it touches almost all of us in the HCV community in some way. I can’t even begin to list all of the emails I receive from people who do not have insurance or who have insurance but do not have enough coverage to pay for HCV care and medications.

HCV PIPELINE

HCV Pipeline: It’s not surprising that the most important HCV-related news stories in 2009 involved the medications being developed to treat hepatitis C. The two drugs that are furthest along in development are the HCV protease inhibitors telaprevir and boceprevir tested in studies with the combination of pegylated interferon plus ribavirin. Both drugs will finish their development cycle in 2010 and the phase III data is expected to be sent to the Food and Drug Administration (FDA) for marketing approval in 2010-2011. It is possible that the FDA may approve the drugs by 2011 – that is if there are no glitches in the data and if the FDA doesn’t have any important safety or other concerns that are not addressed in the clinical studies.

• Telaprevir (with pegylated interferon and ribavirin): Seems to be the winner on the basis of clinical results and outcomes. Genotype 1 treatment-naïve: In 2009 data from various clinical trials of telaprevir, pegylated interferon plus ribavirin (phase II) found that 69% of genotype 1 treatment-naïve patients treated for 24 weeks achieved an SVR. Re-treatment of people who did not achieve an SVR with a previous course of pegylated interferon plus ribavirin for 48 weeks resulted in SVR rates between 38% and 76% (depending of type of prior non-SVR). The most prominent side effect was skin rash. Another study evaluated the current dosing schedule of thrice daily (current phase III studies) and compared it to a twice daily dosing schedule (with the same daily drug exposure). The twice-a-day dose was found to be as effective as the thrice daily dose. The implications of the results are not completely clear at this time since all the previous studies and the current phase III studies of telaprevir are using the thrice daily dose.

• Boceprevir (with pegylated interferon and ribavirin): Close on the heels of telaprevir in clinical development. The phase III studies are fully enrolled and they are expected to be completed in 2010. Merck/Schering is expected to apply to the FDA in 2011. Treatment-naïve HCV genotype 1 patients treated for 48 weeks with a combination of boceprevir, pegylated interferon plus ribavirin achieved an SVR of 75%. A small 48 week re-treatment study of boceprevir and pegylated interferon plus ribavirin in people who did not achieve an SVR resulted in an SVR of 55%. The most worrisome side effect of boceprevir is anemia, which is already a problem in ribavirin containing regimes.

• INFORM-1: This study is the first combination HCV therapy of an HCV protease inhibitor (RG7227) and an HCV polymerase inhibitor (RG7128) without interferon and ribavirin. Very early data is quite encouraging with dramatic drops in HCV RNA (viral load). Unfortunately, the 900 mg dose was eliminated from the study due to adverse events so it is unclear what this means for future studies of the combination therapy.

• Albuferon (Zalbin): Human Genome Science’s (HGS) long lasting interferon (dosed every two weeks) tested in combination with ribavirin completed phase III studies and was deemed to be non-inferior to Pegasys (once-a-week dosing) plus ribavirin. Late in 2009, HGS submitted the data to the FDA for marketing approval. Approval is expected in 2010-2011. How this newer long-acting medication will change the landscape of HCV treatment is unclear.

Other important stories this year (no particular order of importance) include:

• Death of a liver cell: It has long been thought that the immune system attacking the hepatitis C virus infecting liver cells was the cause of liver cell death. Researchers from the University of Alberta, Canada, however, have discovered and reported in early 2009 that HCV itself causes some damage to the liver cell and can lead to the death of liver cells.

• Acquisitions: Two big HCV pharmaceutical companies, Roche and Schering, were acquired or merged in 2009. Roche acquired Genentech earlier this year and has already completed a move from Nutley, NJ to South San Francisco, CA. Merck acquired Schering-Plough in early 2009. Merck and Schering will not be fully merged until the beginning of 2010.

• Liver Transplantation: There was much news in 2009 about liver transplantation. Unfortunately, most of the news was about disparities in care and outcomes were negative.

A study that followed 144,507 patients hospitalized in PA with liver-related conditions of whom 4,361 received a liver transplant evaluation and were waitlisted and of these 1,537 received a liver transplant. The authors found that “61 percent of men were evaluated for transplantation compared to 39 percent of women; 73.8 percent of whites were evaluated compared to 8.6 percent of blacks; and 62 percent of patients who had commercial health insurance were evaluated compared to 4.7 percent with Medicare health insurance only.” (www.urbanmecca.net)

A review of records between 1999 and 2008 from 5 transplant centers that included 771 patient records found that there was a 30% higher mortality rate for African Americans compared to whites. The researchers stated that African Americans had more inflammation and severe fibrosis progression compared to whites who were undergoing a liver transplant. (www.medicalnewstoday.com September issue of Liver Transplantation)

In a study of 850 patients who received a liver transplant from March 2002 through December 2007 for HCV-related liver disease, women were found to have worse outcomes following liver transplantation compared to men. (www.AASLD.org )

• Legislation: 2009 was really the year that the HBV and HCV communities bonded. In 2009, “The Viral Hepatitis and Liver Cancer Control Act,” was introduced by Congressman Mike Honda (D-CA) and Congressman Charles Dent (R-PA). This legislation strives to provide $90 million in funding in 2011 to increase the capacity and ability of the Centers for Disease Control to support state efforts in prevention, immunization and surveillance. We should all be focusing our advocacy efforts to support this very important bill that could help to address some of the disparities in care of HBV and HCV.

• Reports: Two important reports were released in 2009: The first, “Silent Epidemic of Viral Hepatitis May Lead to Boom in Serious Liver Disease,” stated that less than 1 in 5 hepatitis C patients (that’s 663,000 out of the 3.9 million who have HCV in US) are receiving HCV treatment. Breaking it down by total new prescriptions filled—126,000 prescriptions of pegylated interferon plus ribavirin in 2002 fell to 83,000 in 2007. The researchers chalked up the decline in prescriptions to lack of diagnosis of HCV and to the fact that fewer than 25% of the patients diagnosed with HCV were referred for HCV antiviral therapy. Another important report released in 2009 was the Consequences of Hepatitis C Virus (HCV): Cost of a Boomer Epidemic of Liver Disease commissioned by Vertex Pharmaceuticals, Inc. and produced by Milliman, Inc. In their detailed report they confirmed previous estimates of the future disease burden of HCV and came to some alarming conclusions:

The annual cost of advanced liver disease will climb to $85 billion in the next two decades

Medicare costs will increase 500%, from $5 billion to $30 billion in the next two decades

These reports will, hopefully, help reinforce the need for immediate passage of the viral hepatitis legislation listed above.

• HIV and Acute HCV: In the last few years there have been numerous reports of sexual transmission of HCV among HIV positive men. In 2009, a study was released that concluded that sexual transmission and not injection drug use was the cause of acute HCV transmission among HIV positive men in New York. It was also reported that, in the HIV positive men who contracted acute HCV, their HCV disease progression was greatly accelerated and recommended immediate treatment with HCV antiviral medications since the majority of people with acute HCV can rid themselves of the virus. Based on the acute outbreaks of HCV in HIV positive men, New York now considers HCV a sexually transmitted disease—at least among HIV positive men. But it is worth mentioning (at least at this time) that the high rate of sexual transmission has only been seen in HIV positive men and the mode of transmission seems to be related to anal receptive sexual practices.

• Metabolic Syndrome and Steatosis: More and more attention is focusing on the universal effects of metabolic syndrome and particularly steatosis. It is expected that steatosis in the next couple of decades will replace HCV as the number one indication for liver transplantation. If you add metabolic syndrome to HCV you have a scary picture of more serious disease progression and lower treatment outcomes. The bad news about steatosis is that currently there are no medications to treat it, but the good news is that it can be successfully treated in most people through healthy diet and exercise. Notice that I said it can be treated and I didn’t say it is easy. But equipped with all the tools needed, eating and maintaining a healthy diet and exercise program is very achievable.

• Treatment Outcome: People with HCV who achieve an SVR will need to receive follow-up medical care over time because some, especially those who were treated and had severe fibrosis or cirrhosis, may have serious disease progression even after achieving an SVR. The take home message on this news is that while the vast majority of people who achieve an SVR will not have any further serious disease progression, some, unfortunately, will continue to have disease progression.

• Unsafe Injections: Exposed thousands to HCV. In early 2009 a report was released which found that there were at least 60,000 people who may have been exposed to hepatitis B and C in the USA alone. (www.newsday.com) Last year it was the Las Vegas outbreak that put 40,000 people at risk. This year is a bit better, but still any exposure is too many—the largest outbreak was at various Veteran medical centers across the U.S. that was estimated to expose 11,000 people to hepatitis B, hepatitis C and HIV from receiving colonoscopies with equipment that was not sterilized. It is amazing that such widespread outbreaks still occur because standard safety practices that have been set up to protect people are not followed.

• Needle Exchange: On a good note, we are on the brink (as of publication) of finally funding needle exchange in this country. The U.S. House of Representatives and the U.S. Senate have passed the legislation and have included funding of needle exchange in the 2010 Federal budget. President Obama is expected to sign the legislation into law. The tide is finally turning regarding the message about needle exchange—that is, it is about preventing disease transmission rather than the falsely perceived notion of encouraging or condoning drug use. Another shift is taking place in the War on Drugs, which has proven to be a failure on almost every level both domestically and internationally. A different approach in this country and around the world could help us reduce the prison population and work within our country to put in place effective measures that would help with possible solutions to drug addiction.

• Growing Liver Cells from Human Skin: The article that was the most interesting to many of us at HCSP was on growing liver cells from human skin! S.A. Duncan and colleagues from The Medical College of Wisconsin in Milwaukee were able to build on previous research led by J. Thomson and colleagues at University of Wisconsin-Madison by manipulating skin cells to form liver cells. The potential of creating liver cells from skin cells will help speed up new tests, drug development, including vaccines, and may even lead to technology that will enable us to completely regenerate a liver. Keep your eyes on this discovery—you will be hearing about this for years to come as a critical point in the science of the liver.

Honorable mention goes to wonderful caffeine where yet another inspiring study has found that drinking coffee may lower the risk of disease progression. The study was part of the HALT-C study. Kidding aside, the study was a self-disclosure study that asked people how much coffee they drank. The actual coffee and caffeine consumption (that is how much caffeine was present in each cup of Joe) was not scientifically evaluated so the take home message on this study: moderate coffee consumption is probably ok for the liver. It would be interesting, though, if a well-designed prospective clinical trial on coffee and caffeine was conducted to determine exactly the benefits and risks, if any, of caffeine consumption.

We would be interested in how you rate the stories, that is, in order of importance. Drop us a line and let us know and include any items you believe that should have been incorporated into our list.

One can only hope that at this time next year (which will be here faster than a speeding bullet) we will be debating about what needs to be improved in the healthcare reform bill that was enacted into law in 2010.

How do you handle having chronic hepatitis C virus infection (HCV)? Are you the kind of person who dives into the Internet, searching for information? Are you looking for the latest treatment or herbal supplement? Have you made lifestyle changes, focusing on healthy choices, such as nutrition and exercise? Or, are you overwhelmed, tired, or confused and have taken up permanent residence on the couch? Perhaps, you have decided to ignore HCV altogether.

If what you are doing works for you, read no further. However, if like me, you feel there is room for improvement in your health regimen, keep reading. This month’s Healthwise focuses on a proven health-enhancing strategy that has helped many. It’s called physical activity, also known as exercise.

My level of physical activity drops in the winter. A little rain or snow keeps me indoors. I don’t ski or have a condo in Hawaii. I confess, I don’t own any aerobic equipment, although I encourage others to use it. Our local gym has a monthly membership option with no initiation fee, so I join up in the winter. When snow keeps me home from the gym, I shovel the driveway instead.

To some with HCV, the thought of exercise seems monumental—like climbing a mountain. It was like this for me when I first contracted HCV. However, I had it backwards. I didn’t need to feel good in order to exercise; I needed to exercise in order to feel good. That meant that I had to start the process when I didn’t feel like it.

Once I got into a fitness routine, I noticed how good I felt, although not right way. In fact, at first it was pretty lousy. The only thing that felt good about exercising was having done it. Eventually, the benefits kicked in. Now it is so much a part of my life that I can’t go long without it.

So how do you get started? Begin with your medical provider. Always make sure there isn’t a health reason preventing you from exercise. I was secretly wishing that my doctor would tell me that I could never exercise but that I should eat chocolate instead.

Your medical provider may offer suggestions for beginning a fitness program. If not, you are on your own. Here are some tips to help you get started during the winter months:

Make a list of the benefits of exercise. Use this list if you find yourself making excuses to slack off. For those with HCV, exercise may reduce fatty liver, lower risk of diabetes, and enhance immune response. In general, physical fitness prevents bone loss, lowers cholesterol, helps with muscle aches and improves overall health. It is also good for depression and insomnia. These are just a few of the potential benefits.

Start small and slow. This is a commitment to your health. You are more likely to stay with it if it isn’t torture.

Set short-term and long term goals. These should be specific, obtainable, and easy to measure. Here are examples:

Long-term goal—Do ten push-ups by the end of 2010.

Short-term goal—Do five modified push-ups every other day for one week.

Long-term goal—Walk 3 miles, five days a week by the time of my high school reunion.

Short-term goal—five days this week, walk around the block.

Evaluate your progress. If you met your goal, great. Perhaps you want to set a slightly bigger goal. If you didn’t meet it, why not? Was it too big? Did you have reasonable obstacles? Did you have good intentions but just couldn’t get going? Examine the reasons without criticizing yourself. The goal is to find a way to increase physical fitness; it isn’t a time to induce guilt. Guilt will keep you on the couch.

Reward yourself for your effort. Tell yourself you are doing a good job. Never criticize any effort as long as you are trying. You can create incentives, such as: if I exercise twenty days in the month, I will buy tickets to an event. Even better, buy yourself something sports-related, such as a heart rate monitor or fitness attire.

Schedule it in. Most people find that when they exercise first thing in the morning, they are likely to do it. Left until later in the day, it’s easy to put off. I prefer to exercise in the afternoon. It helps me to let go of my work day, reenergizes me and helps me sleep better.

Prioritize. If exercise is one of your highest priorities, you are less likely to skip it.

Look into programs that suit your needs and budget. For instance, some Medicare plans offer free gym membership through the SilverSneakers program.

Make it the law. When exercise is a non-negotiable contract with yourself, then you are more likely to keep it up.

Have fun and be creative. Exercise isn’t a four-letter word, unless it’s yoga. Why not make it playful? Make it a social event. Start a walking club in your neighborhood. Instead of meeting friends for lunch, go for a walk. Volunteer to walk dogs at your local animal shelter. Take a dance class. If it rains, put on boots and a waterproof jacket and splash in the puddles. Go play in the snow.

Think outside the box. Exercise doesn’t have to be all or nothing. Doing six activities for 5 minutes each is the same as doing 30 minutes of the same activity. The website, Squeeze-It-In, has exercises you can perform in all sorts of places, including the car.

Use the number one most effective exercise equipment—a journal. Studies show that those who use journals to record goals and keep track of their progress are more likely to reach their fitness objectives. A simple calendar or pad of paper is all you need. There are online journals that help organize and analyze your fitness routine.

You don’t need to spend money on physical fitness. If you have Internet, there are free videos for a variety of activities. Check out LiveStrong, RealAge and YouTube. If you aren’t an Internet user, look for these at your library.

Be sensible about exercise. If you are wondering about stretching, the recommendations are to stretch dynamically rather than statically. Remember to drink water, apply sunscreen and avoid injuries. Pain is NOT gain. However, sore muscles may occur. Heat and cold packs may be beneficial. Remember to consult a doctor for injuries and discuss a back-up fitness plan if you can’t do your regular routine. Avoid exercise when ill, especially if you have a fever.

There are endless excuses for not exercising, but excuses are just problems waiting to be solved. No time? Exercise makes us more efficient. Besides, illness is a huge time-eater. If your excuses keep getting in the way of your success, take a look at them. Alternatively, you can skip the excuses and just do it. I doubt you will regret it.

Resources

American Association of Retired People (AARP) www.aarp.org/healthAARP and Carole Carson developed Fat 2 Fit, an online version based on her book, From Fat to Fit. Anyone may join.

LiveStrong www.livestrong.com Started by cyclist and cancer survivor Lance Armstrong, this organization provides tons of information and free fitness videos.

Quality of Life: Effects of Hepatitis C and Its Treatment—Liz Highleyman

Quality of life is an important issue for people with chronic hepatitis C. While HCV can cause advanced liver disease after years or decades, the virus itself and the drugs used to treat it may have detrimental effects on quality of life at much earlier stages of disease.

Overall health, physical and mental functioning, and the ability to carry out desired activities all play a role in quality of life. Investigators use a variety of standardized instruments to measure different aspects or “domains” of quality of life in controlled studies, but research can be difficult due to its subjective nature and wide variability across individuals.

Several recent journal articles and conference presentations have looked at various aspects of quality of life among people with hepatitis C and the impact of interferon-based therapy.

SUSTAINED RESPONSE IMPROVES QUALITY OF LIFE

People with HCV often experience symptoms that interfere with quality of life well before serious liver damage occurs. As described below, for example, HCV in the brain may cause neurocognitive impairment. As such, effective therapy that fully suppresses the virus may result in improved quality of life.

As reported in the October 2009 American Journal of Gastroenterology, A.A. John-Baptiste from the University of Toronto and colleagues assessed the health status of 133 hepatitis C patients who achieved sustained virological response (SVR) six months after completion of interferon-based therapy, compared with that of 102 nonresponders.

After an average of 3.7 years following treatment, participants responded to a variety of standardized health-related quality of life and preference/utility measures either as written surveys by mail or in-person interviews including the Hepatitis-specific Medical Outcomes Study, the Short-Form 36-Item Health Survey, the Health Utilities Index Mark 2/3 (HUI-2/3), and the Time Trade-off (TTO) for current health.

Treatment nonresponders had significantly lower scores on the eight SF-36 domains, lower scores on hepatitis-specific domains, and lower physical and mental component summary scores compared with those who achieved SVR. Nonresponders also had significantly lower scores using other measures, although differences in HUI-2 and TTO scores were no longer statistically significant after adjusting for demographic and clinical factors.

In addition, 44% of treatment nonresponders said they missed work, volunteer opportunities, or household activities due to hepatitis C or its treatment, compared with just 9% of sustained responders.

“Patients with a sustained response to antiviral therapy for chronic HCV infection have better quality of life than treatment failures do,” the researchers concluded. “Our study validates the benefits associated with the sustained response to antiviral therapy in a real-world clinic population and shows that these benefits are maintained over the long term.”

NEUROCOGNITIVE IMPAIRMENT

In the September 2009 Journal of Viral Hepatitis, G.R. Foster from Queen Mary’s University of London provided an overview of health-related quality of life among people with HCV, focusing on cognitive and mental health concerns.

Fatigue, depression, and neurocognitive problems such as poor concentration are among the most common reported complaints, he noted. Many people with HCV experience “brain fog” long before they develop hepatic encephalopathy due to liver decompensation.

Replicating HCV has been found in central nervous system tissue, and changes in neurotransmitter levels in the frontal white matter of the brain are associated with impaired attention and concentration in people with hepatitis C, according to Foster.

In a related study described in the September 15, 2009, advance online edition of the Journal of Viral Hepatitis, D. Lowry from Mater Misericordiae University Hospital in Dublin looked at health-related quality of life, mood, and neuropsychological test performance in a cohort of Irish women with mild histological liver disease.

The 20 HCV positive study participants were infected via medical procedures (iatrogenic infection) and did not have comorbidities and risk factors (such as injection drug use) that can contribute to neurocognitive impairment; nine healthy HCV negative women were included as control subjects.

In conclusion, the researchers wrote, “these findings appear to support the presence of neurocognitive abnormalities in an iatrogenically infected, homogeneous female HCV population who were carefully screened to eliminate other factors affecting neurocognitive test performance and may indicate underlying neurophysiological causative mechanisms.”

DEPRESSION

Depression is a well-known side effect of interferon that can have a major detrimental effect on quality of life. As reported in the December 2009 American Journal of Gastroenterology, D.M. Evon and colleagues with the Virahep-C Study Group analyzed the association between patient characteristics, depression before and during therapy, and treatment outcomes. Virahep-C was designed to look at factors affecting response to pegylated interferon alfa-2a (Pegasys) plus weight-adjusted ribavirin, with a focus on racial differences.

In this analysis, which included 203 white and 191 black patients, the researchers used the Center for Epidemiologic Studies Depression (CES-D) scale to measure depression before and during therapy and six months after the end of treatment.

Before starting therapy, 12% of participants had CES-D scores indicating depression (23 or higher). Having less social support was a significant risk factor for pretreatment depression. During treatment, these patients were more likely to experience psychiatric adverse events or start antidepressants (45% vs. 28%) and to discontinue treatment early (38% vs. 13%). Nevertheless, patients with and without depression prior to treatment had similar SVR rates (38% vs. 40%, respectively).

By week 24, 26% had developed new-onset depression. One-third started antidepressants; none attempted suicide. Incident depression was significantly associated with younger age and having less social support. Participants who developed depression during treatment were more likely to experience psychiatric adverse events or start antidepressants (44% vs. 23%). However, newly depressed patients had a lower likelihood of treatment discontinuation (6% vs. 15%), and again SVR rates were comparable (47% vs. 38%).

SLEEP DISTURBANCES

Inadequate sleep is associated with a host of mental and physical manifestations, and can impair quality of life. In the September 1, 2009, advance online Journal of Clinical Gastroenterology, S. Sockalingam from the University of Toronto and colleagues presented a review of sleep problems in people with hepatitis C.

Sleep disturbances occur in up to 60% of individuals with chronic hepatitis C and are often accompanied by comorbid psychiatric disorders, the researchers wrote. In addition to the effects of HCV infection itself, interferon-based therapy also leads to sleep problems in approximately 30% of treated patients.

Insomnia in patients with HCV may be worsened by psychiatric conditions such as depression and physical conditions such as anemia or hypothyroidism. Therefore, the researchers wrote, “prompt recognition using screening tools and exclusion of comorbid conditions contributing to sleep pathology can enhance treatment outcomes.”

SEXUAL DESIRE AND FUNCTION

Interferon-based therapy can also cause sexual problems, according to study published in the September 2009 Gastroenterology. L.M. Dove and colleagues, also with the Virahep-C Study Group, looked at the impact of antiviral therapy on male sexual health.

This analysis included 260 men with HCV genotype 1 (half white and half black; median age about 50 years). Before starting therapy, 37% reported some degree of impaired sexual desire, 44% reported dissatisfaction with their sex life, 26% reported impaired erectile function, and 22% reported impaired ejaculation. During treatment, the men experienced significant declines in all components of sexual health, and by the end of therapy, 38% to 48% reported that their overall sexual functioning was worse. Compared with whites, black men reported less impairment in sexual desire or satisfaction during therapy.

By 24 weeks after treatment, however, sexual desire and satisfaction had improved, reaching levels similar to those at baseline. However, more men reported persistent erectile or ejaculatory problems after completing treatment than before starting.

The researchers concluded that, “Sexual impairment is common among men with chronic hepatitis C undergoing therapy with pegylated interferon and ribavirin and should be considered as a potential side effect of antiviral therapy.”

TREATMENT BENEFITS OUTWEIGH DRAWBACKS

Taken together, these studies suggest that while interferon-based therapy may temporarily worsen health-related quality of life due to side effects, patients who achieve sustained response ultimately experience improved quality of life.

“Although treatment-related adverse effects may dissuade people from starting therapy and reduce compliance with associated reductions in sustained viral response, for the majority of patients viral clearance produces improvements in both health-related quality of life and long-term prognosis,” Foster concluded in his review.

New treatments including several directly targeted anti-HCV agents now in the development pipeline may allow for reducing the duration of interferon therapy, or possibly eliminate it altogether.

Finally, individual attitude can be a major determinant of quality of life. As Lucinda K. Porter reported in the December 2009 HCV Advocate, Italian researchers presented data at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) this past fall indicating that on the whole, hepatitis C patients including prior treatment nonresponders or relapsers have good overall quality of life.

C. Selmi from the University of Milan and colleagues concluded that, “patients with chronic hepatitis C manifest a strong resilience and a well-preserved quality of social relationships and psychological well-being which ultimately maintain high degrees of quality of life.”

They added that informing people about the natural history of the disease is “critical to patient quality of life and should not be overlooked when new treatments are proposed.”

Similarly, Dove’s group advised that people considering treatment should be counseled about the possibility of decreased sexual function during therapy. This recommendation applies to all side effects that can diminish quality of life, along with reassurance that if treatment is effective, daily life is likely to improve.

References

John-Baptiste, A.A. et al. Sustained responders have better quality of life and productivity compared with treatment failures long after antiviral therapy for hepatitis C. American Journal of Gastroenterology. 104(10): 2439-2448. October 2009.

Foster, G.R. Quality of life considerations for patients with chronic hepatitis C. Journal of Viral Hepatitis 16(9): 605-611. September 2009.

In the article “AASLD 2009: Part 1” in last month’s HCV Advocate newsletter, I discussed the top performers in the new class of HCV direct antivirals—telaprevir, boceprevir and the INFORM-1 combination trial. In “AASLD 2009: Part 2” I will discuss some of the many new drugs that are being developed to treat hepatitis C. The drugs listed below are in very early development (Phase I and Phase II) so the data presented here will be very brief.

HCV PROTEASE INHIBITORS

PHX1766: In a study of healthy volunteers and HCV genotype 1 patients who were given PHX1766 it was found that the average maximal HCV RNA decline after 6 days was -1.2 log10 in the 400mg BID group and -1.8 log10 in the 800mg BID group. PHX1766 was generally well-tolerated. One serious adverse event was reported, but the investigators believed that it was unrelated to the study drug.

MK-7009: Updated information about the ongoing trial was presented. The proportion of subjects who achieved RVR in the MK-7009-containing arms ranged from 69% to 82%, vs. 6% in the placebo group, and the percentage of patients who achieved an EVR ranged from 76 to 89% compared to 60% in the placebo group. No serious adverse events resulted in treatment discontinuation.

TMC435: A study of prior non-responders and treatment-experienced patients found that at day 28, all four patients who completed treatment achieved HCV RNA <25 IU/mL with an overall mean change from baseline of- 5.86 log10 IU/mL. Three of those four patients had HCV RNA below the lower limit of detection (<10 IU/mL) at day 28.

POLYMERASE INHIBITORS

Narlaprevir: Two studies of narlaprevir were presented at AASLD. In the first study, participants were given narlaprevir (twice daily or thrice daily; with and without ritonavir) and PegIntron for 2 weeks followed by PegIntron plus ribavirin for 24 or 48 weeks. A total of 41 (20 treatment-naïve; 21 treatment-experienced) HCV genotype 1 patients were treated. The sustained virological response rates were 81% (13 of 16 patients) in the treatment-naïve group; 17% (1 of 6 patients) in the prior non-responder group; and 50% (5 out of 10 patients) in the group who were prior relapsers. The side effect profile was consistent with side effects seen with pegylated interferon plus ribavirin therapy. The results of this study showing potent antiviral activity of narlaprevir when combined with ritonavir prompted the design of the second study combining a once-a-day dose of narlaprevir with ritonavir.

In the second study, a total of 111 HCV genotype 1 treatment-naïve patients were randomized into 6 groups with different doses of narlaprevir, ritonavir, and PegIntron plus ribavirin.

It was found that the 200 mg/ 400 mg narlaprevir/ritonavir once-a-day groups achieved undetectable HCV-RNA levels at week 4 in 58-87% of patients and at week 12 in 84-87% of patients. Narlaprevir/ritonavir was found to be generally safe and well-tolerated. There was an increased frequency of anemia compared to the group that did not receive narlaprevir/ritonavir. A total of 20 patients discontinued treatment due to side effects—12 to 16% in the narlaprevir arms vs. 39% in the PegIntron plus ribavirin control group.

MK-3281: Twenty-two HCV genotype 1 a/b and genotype 3 male treatment-naïve patients and treatment-experienced patients were treated with MK-3281 monotherapy for 7 days. There was up to a 3.75 log10 (-1.28 to – 3.75) decrease in HCV RNA. The best antiviral response was seen in HCV genotype 1b patients (-3.75 log10). The drug was generally safe and well-tolerated. The most common side effects reported were headache, migraine, dizziness, tiredness, loss of libido, and abdominal pain.

PSI-7851: Results from a multiple dose (50mg, 100mg, 200mg or 400mg) study of 40 treatment-naive HCV genotype 1 patients who were treated with PSI-7851 mono therapy for 3 days were presented. A dose-dependent HCV RNA decline of up to -1.95 log10 IU/mL was observed. The drug was generally well-tolerated for the short period of time it was given. Additional studies of PSI-7851 in combination with pegylated interferon plus ribavirin are being planned.

ABT-333: 41.7% (10 out of 24 patients) who were treated for 28 days with ABT-333 plus pegylated interferon and ribavirin after 28 days of treatment had less than 25 IU/mL HCV RNA (viral load) compared to none out of 6 patients in the placebo, pegylated interferon/ribavirin arm (without ABT-333) for 28 days.

The side effects were reported to be mild in severity (85%) with 63% believed to be from pegylated interferon/ribavirin. There were no serious adverse events or discontinuations due to adverse events.

IDX184: A three-day, phase I proof-of-concept study evaluating the safety and antiviral activity of IDX184 (monotherapy) enrolled 41 treatment-naive HCV genotype 1-infected patients into four dosing groups (25 mg, 50 mg, 75 mg and 100 mg). Mean viral load decreases ranged from 0.47 log10 in the 25 mg group to 0.74 log10 in the 100 mg group after three days of treatment. IDX184 was well-tolerated in this study with no serious adverse events reported and no discontinuations from the study. Idenix announced that it has begun a phase II study of IDX184 in combination with pegylated interferon and ribavirin.

BI 207127: In a small trial of 60 HCV genotype 1 treatment-naïve patients, BI 207127 was found to be a potent inhibitor of viral replication in monotherapy, causing a sharp decline of viral load at 800 mg every 8 hours in the first 24 hours (5/9 patients with > 4 log10 reduction at Day 5, and no viral load breakthroughs). BI 207127 was generally safe and well-tolerated in this study; the only drug-related severe adverse event, a moderate erythema (red skin/rash), was managed effectively. Two other cases of mild transient rash occurred, but it did not require BI 207127 dose reduction or discontinuation. A 4-week combination study with doses of BI 207127 up to 800 mg thrice daily in combination with pegylated interferon and ribavirin will be completed in the 4th quarter of 2009.

THERAPEUTIC VACCINE

GI-5005: There was a report from an ongoing Phase 2b study to compare GI-5005 plus pegylated interferon and ribavirin versus pegylated interferon plus ribavirin alone (without GI-5005) in 140 HCV genotype 1 patients who were either treatment-naïve or prior non-responders produced modest results. On a modified intent-to-treat basis (patients having received at least one dose of combination therapy), treatment-naïve patients receiving GI-5005 plus Peg/ribavirin as a triple therapy had an end-of-treatment complete response rate (HCV RNA < 25 IU/mL by PCR assay at 48 weeks) of 74%, compared with an end-of-treatment response rate of 59% for treatment-naïve patients receiving pegylated interferon/ribavirin (without GI-5005).